De-Escalated Adjuvant and Definitive Radiation Therapy Informed by DART 2.0 ctHPV-DNA
DART 2.0: ctHPV-DNA Informed De-Escalated Adjuvant and Definitive Radiation Therapy
3 other identifiers
interventional
455
1 country
3
Brief Summary
This phase II trial examines the use of blood-based biomarkers is to help inform decision making for treatment and radiation therapy for patients with human papillomavirus (HPV) positive oropharyngeal squamous cell cancers. The standard treatments for head and neck cancers are radiation therapy with chemotherapy or surgery potentially followed by radiation therapy with or without chemotherapy. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving chemotherapy along with radiation may kill more tumor cells. However, the cancer can recur or can spread to other parts of the body and all treatments can be associated with side effects. The purpose of this study is to evaluate a blood-based biomarker, using the NavDx testing device, for head and neck cancers in order to see if it can help improve selection of the intensity of treatment in order to best balance the side effects of treatment with the goal of decreasing cancer recurrence. This test could aid in early detection of recurrence and salvage therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2023
Longer than P75 for phase_2
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 30, 2022
CompletedFirst Posted
Study publicly available on registry
September 15, 2022
CompletedStudy Start
First participant enrolled
February 21, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 1, 2029
May 12, 2026
May 1, 2026
5.4 years
August 30, 2022
May 8, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS)
Progression-free survival (PFS), the time from treatment initiation until disease progression or worsening. PFS at specific timepoints will be estimated using Kaplan-Meier methodology.
From registration to the first of either disease progression/recurrence or death, assessed up to 5 years
Secondary Outcomes (18)
Progression-free survival (PFS) follow-up
At years 1, 2, 3, 4, and 5
Disease-free survival (DFS)
From time of surgery and also from end of all treatment across all the groups, assessed up to 5 years
Overall survival (OS)
At years 1, 2, 3, 4, and 5
Patient reported outcomes (PROs)
Up to 5 years
Incidence of adverse events
Up to 5 years
- +13 more secondary outcomes
Other Outcomes (7)
ctHPVDNA detectability
At post-operative day 1 or 2
Salivary ctHPVDNA analysis for recurrence risk and surveillance
Up to 5 years
Characterization of post-operative drain fluid
Up to 5 years
- +4 more other outcomes
Study Arms (4)
Group 1 (observation)
ACTIVE COMPARATORPatients undergo observation following standard of care surgery. Patients undergo modified barium swallow study (MBSS) at pre-op, 2 weeks post-op, and 3 months follow-up. Patients also undergo CT, PET/CT, or magnetic MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
Group 2 (DART, docetaxel)
EXPERIMENTALPatients undergo DART with/without mucosal sparing BID on days 1-12 Monday-Friday for a total of 20 fractions within 8 weeks of standard of care surgery. Patients receive concurrent docetaxel IV over 1 hour on days 1 and 8 (Mondays preferred). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, 2 weeks post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
Group 3 (IMRT/IMPT, with/without cisplatin)
EXPERIMENTALPatients undergo IMRT or IMPT QD on days 1-40 Monday-Friday for a total of 30 fractions within 6 weeks of standard of care surgery. Depending on risk status, patients may also receive concurrent cisplatin IV over 1-2 hours once a week QW on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, 2 weeks post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
Group 4 (IMRT/IMPT, cisplatin)
EXPERIMENTALPatients undergo IMRT or IMPT therapy QD on days 1-40 Monday-Friday for 28 or 35 fractions based on biomarker response along with concurrent cisplatin IV over 1-2 hours QW on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS prior to RT and at 3 and 12 months post RT. Patients undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing pre-RT, 4 weeks into RT, anticipated fraction 20, end of RT, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
Interventions
Undergo blood and saliva specimen collection for NavDx testing
Given IV
Undergo CT scan
Undergo DART
Given IV
Undergo IMPT
Undergo IMRT
Undergo MRI
Undergo MBSS
Undergo PET scan
Ancillary studies
Ancillary studies
Eligibility Criteria
You may qualify if:
- PRE-REGISTRATION (optional): Provide written informed consent
- Age \>= 18 years
- Histological confirmation of squamous cell carcinoma originating from or suspected to be originating from the oropharynx
- Plan for gross total surgical resection via trans oral surgery with curative intent and at least unilateral neck dissection OR chemoradiotherapy with cisplatin. Note: The patient must be cisplatin eligible even if an alternate is used due to drug shortage
- Absence of distant metastases on standard diagnostic work-up =\< 16 weeks prior to registration. (Chest CT or PET/CT)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 1
- Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
- Ability to complete questionnaire(s) by themselves or with assistance
- Provide written informed consent
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- Willing to provide blood samples for correlative research purposes, including anonymous shipment of samples to for NavDx testing
You may not qualify if:
- Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)+
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- Other active malignancy =\< 5 years prior to registration. EXCEPTIONS: Nonmelanotic skin cancer or carcinoma-in-situ of the cervix, or prostate or localized endometrioid endometrial cancer. NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
- Prior history of radiation therapy to the affected site
- Prior systemic chemotherapy in the last 5 years
- Contraindication to radiation therapy as determined by the treating team
- History of allergic reaction to docetaxel
- Receiving any medications or substances which in the opinion of the investigators would interfere with treatment. Examples could include strong inhibitors of cytochrome P450 3A4 (CYP3A4) at oncologist discretion
- Severe pre-existing ototoxicity or neuropathy that would, in the opinion of the investigator, preclude the use of cisplatin chemotherapy
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
Study Sites (3)
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
David M, Routman, M.D.
Mayo Clinic in Rochester
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 30, 2022
First Posted
September 15, 2022
Study Start
February 21, 2023
Primary Completion (Estimated)
August 1, 2028
Study Completion (Estimated)
August 1, 2029
Last Updated
May 12, 2026
Record last verified: 2026-05